--Mechanisms of Chlamydial Manipulation of Host Cell Apoptosis-- Chlamydial infection in humans imposes a major health problem in both developing and developed nations. Urogenital tract infection with C. trachomatis species is a leading cause of sexually transmitted bacterial diseases and is also linked to certain type of cervical carcinoma while respiratory infection with C. pneumoniae species is associated with atherosclerosis, a major vascular condition for cardio-cerebral fatality. Although the species C. psittaci is primarily an animal pathogen, humans are also susceptible to C. psittaci infection, developing life-threatening pneumonia. Since humans can acquire infection via aerosolized animal feces that are contaminated with C. psittaci organisms, CDC has once listed C. psittaci as a category B agent for biodefense. These chlamydia-induced or -associated pathologies are largely due to Chlamydial ability to either productively replicate or to achieve a long-term persistence within a cytoplasmic vacuole of eukaryotic cells, which are aided by the Chlamydial unique intracellular biphasic life cycle and the Chlamydial ability to evade host defense. The current proposal is designed to understand how chlamydia evades a very important host defense effector mechanism-apoptosis. We have previously demonstrated that chlamydia possesses a potent anti-apoptotic activity, which may contribute to the Chlamydial ability to survive in the infected hosts for long periods of time. By identifying the molecule(s) responsible for the Chlamydial anti-apoptotic activity and understanding how the anti-apoptotic molecules work as proposed in the current project, we may be able to develop reagents/approaches for blocking the Chlamydial anti-apoptotic activity and preventing chlamydia-induced pathologies. [unreadable] [unreadable]